Pulmonary Effects and Complications of Snakebites Ariaranee Gnanathasan, MPhil, MD; and Chaturaka Rodrigo, MD
This review is on the pulmonary complications of snakebites, which can have fatal consequences. We identiﬁed three common themes as reported in the literature regarding envenomation: generalized neuromuscular paralysis aﬀecting airway and respiratory muscles, pulmonary edema, and pulmonary hemorrhages or thrombosis due to coagulopathy. Respiratory paralysis and pulmonary edema can be due to either elapid or viper bites, whereas pulmonary complications of coagulopathy are exclusively reported with viper bites. The evidence for each complication, timeline of appearance, response to treatment, and details of CHEST 2014; 146(5):1403-1412
pathophysiology are discussed. ABBREVIATIONS:
DIC 5 disseminated intravascular coagulation
The pulmonary complications of snakebites have had little focus in the medical literature, but a significant number of deaths from lung involvement due to systemic envenomation is plausible. In endemic areas, pulmonary involvement in snakebite is commonly encountered in clinical practice; therefore, it is surprising that the number of case
Manuscript received November 12, 2013; revision accepted April 30, 2014. AFFILIATIONS: From the Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka. CORRESPONDENCE TO: Ariaranee Gnanathasan, MPhil, MD, Department of Clinical Medicine, Faculty of Medicine, University of Colombo,
reports and series are lacking. Perhaps in settings where clinicians have accepted it as the norm makes the condition not worth reporting. This review summarizes the effects of snakebite envenomation on lungs and the rest of the respiratory apparatus as reported in the literature to aid clinicians practicing in endemic regions.
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yahoo.com © 2014 AMERICAN COLLEGE OF CHEST PHYSICIANS. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.13-2674
Materials and Methods This narrative review synthesizes PubMed and EMBASE searches with the following key words: “snake bite” in abstracts and (1) “pulmonary” in any field, (2) “ventil*” in any field, and (3) “lung” in any field. The same search strategies were repeated using the key word “snake” instead of “snake bite.” The search was then extended to involve more-specific key words based on the themes identified after the first round of searching (eg, “respiratory paralysis,” “pulmonary edema,” “thromboembolism”). Key words such as “paralysis,” “neurotoxicity,” “intubation,”
Review Venomous snakes to humans are primarily divided into four families: (1) viperidae (. 200 species; responsible for a large number of human deaths; includes vipers, puff adder, and rattlesnakes), (2) elapidae (highly venomous species; includes cobras, sea snakes, coral snakes, and kraits), (3) colubridae (only a few species are potentially harmful), and (4) atractaspididae (a few species can produce cardiotoxic venom).1 Pulmonary involvement during envenomation has been reported in viper and elapid bites and can be categorized into three main themes: (1) respiratory paralysis, (2) pulmonary edema, and (3) hemorrhage and thrombosis involving the pulmonary vasculature. Respiratory Paralysis
Respiratory paralysis, although part of a generalized neuromuscular dysfunction, has two consequent mechanisms specific to the respiratory system that lead to death: (1) accumulation of secretions and paralysis of tongue, causing upper airway obstruction, and (2) paralysis of the diaphragm and intercostal muscles, leading to impaired ventilation and hypoxia. The term “respiratory paralysis” in this article refers to upper airway obstruction by paralysis of oropharyngeal muscles (which can cause death by itself) as well as to paralysis of the ventilatory apparatus by dysfunction of the intercostal muscles and diaphragm. The snakes that cause neuromuscular junction dysfunction are mostly elapids, although vipers also account for a significant number of cases. The neurotoxins in snake venom are usually classified as a and b. a-Neurotoxins cause reversible postsynaptic blockage of acetylcholine receptors by a curare-like action (eg, irditoxin), whereas b-neurotoxins (eg, crotoxin, viperotoxin, taipoxin) cause more lengthy presynaptic blockade by interfering with acetylcholine release.1 Sometimes the venom causes irreversible damage to the presynaptic terminal, and new terminals must form before the effect wears off. Some snakes have both a- and b-neurotoxins in their venom (see next). Although respiratory paralysis is a well-known complica1404 Special Features
“oedema” (“edema”), “anticholinesterases,” “neostigmine,” and names of specific snakes were used in a second search round. The search was restricted to articles published in the past 20 years to get the most recent information. There were 1,506 abstracts in this initial search. The software EndNote 3.0 (Thomson Reuters) was used to filter articles. Bibliographies of cited literature were also searched. All abstracts were read independently by the two authors, and key articles were identified based on a consensus. The final synthesis comprised 72 articles. These were mainly in form of case reports and case series.
tion of snakebites, especially after elapid bites (eg, cobras, kraits), the number of cases reported in the literature are few.2-4 In a case series in Sri Lanka, Theakston et al4 described the clinical course of five patients bitten by common kraits (Bungarus caeruleus) and two patients bitten by Sri Lankan cobras (Naja naja naja). Respiratory paralysis developed in two patients in the series who had to undergo mechanical ventilation. Their symptoms reversed within 8 to 30 h. In another case series of 25 cobra bites in Sri Lanka, Kularatne et al5 described four patients (16%) needing ventilatory support (median duration, 24 h). A case series of 83 children aged 6 months to 12 years with snakebites in Malaysia reported four cases of respiratory failure needing mechanical ventilation. Two of these died, and the other two recovered. In another case series where four patients with cobra bites were managed without administration of antivenom but by mechanical ventilation alone, symptoms reversed within 36 to 72 h.6 Studies characterizing the venom of the Indian cobra (Naja naja), which is similar to its Sri Lankan counterpart, have shown the main venom component to be a phospholipase A2, which acts postsynaptically.7,8 This explains the relatively faster recovery from paralysis caused by cobra bites compared with krait bites. Laothong and Sitprija9 described the course of three patients bitten by Malayan krait (Bungarus candidus) in whom respiratory failure developed. In the absence of specific antivenom, the patients were managed with mechanical ventilation. One died of cardiac arrest and the other two recovered after 4 and 30 days of mechanical ventilation. Administration of acetylcholine esterase inhibitors (neostigmine) was not associated with an immediately apparent benefit. However, this observation was in contrast to that of Warrell et al,10 who also described two patients envenomed by Malayan kraits needing respiratory support. One patient survived, showing a dramatic response to neostigmine. Malayan krait venom contains neurotoxins that cause predominantly
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presynaptic inhibition, explaining the prolonged course of respiratory paralysis. Two small randomized doubleblind trials have shown a positive effect for edrophonium (a short-acting anticholinesterase) in reversing the neuroparalytic effects of Naja philippinensis bites.11,12 In a large prospective study in India, 72 patients with common krait envenoming were treated with antivenom and neostigmine (three doses of 2.5 mg at 30-min intervals).13 The mean time between bite and arrival at the hospital was 4.5 h. All patients proceeded to have respiratory paralysis requiring ventilatory support, and neostigmine did not seem to have an effect on improving the signs of paralysis. However, there was no control arm for comparing duration of ventilation and recovery times. This finding is explainable by looking at the mechanism of action of krait b-neurotoxins that act presynaptically. They lead to the depletion of acetylcholine vesicles, impaired acetylcholine-mediated neurotransmission, and loss of the nerve terminal some time later. Clinical recovery is slow and involves regeneration of the nerve terminal; thus, the patient must be supported with mechanical ventilation until such time. Antivenom and anticholinesterases are unlikely to help offset the effect of already-bound venom.14 The postsynaptically bound neurotoxins vary in their composition, but most produce a curare mimetic nondepolarizing blockage that is potentially reversible by antivenom and anticholinesterases.14 There are a few case reports of bites involving Asiatic cobra, the coral snake Micrurus frontalis, and death adder wherein anticholinesterases reversed neurologic paralysis. The dominant components of venom in these instances would have bound to the postsynaptic membrane.15-18 Again, this is an oversimplification because some molecules (eg, a-bungarotoxin) bind more or less irreversibly to the postsynaptic membrane, and anticholinesterases will have little effect in reversing such envenomations despite the location of action being the postsynaptic membrane. However, several venom toxins (cobrotoxin, candotoxin) bind reversibly to the postsynaptic membrane, leaving a potential role for anticholinesterases. Snake venom comprises multiple molecules with variable actions on either side of the nerve terminals; thus, response to these agents can be highly variable. In a Sri Lankan series of 88 common krait (B caeruleus) bites, Ariaratnam et al19 reported respiratory failure in 56 (64%) (Fig 1). Respiratory failure developed between 30 min and 13 h from the time of the bite. All patients were intubated and mechanically ventilated (mean duration, 5 days; range, 18 h-16 days). In a larger case
Figure 1 – Patient receiving supportive care for respiratory paralysis caused by envenomation by Bungarus caeruleus.
series of 210 patients with common krait bites also from Sri Lanka, Kularatne et al20 showed that 48% needed respiratory support with mechanical ventilation. The mortality rate was 7.6%, and the duration of ventilator dependence varied between 12 h and 29 days (mode, 2 days). Those who were severely envenomed were treated with Indian polyspecific antivenom (Haffkine), but a higher dose of antivenom did not result in a significant reduction in duration of mechanical ventilation. Although the antivenom may clear the unbound venom in blood during the early phase of envenomation, it cannot reverse the damage incurred by the alreadybound venom to nerve terminals. In cases of presynaptic inhibition, new nerve terminals must form to regain functionality, and repeated administration of antivenom is unlikely to help. In fact, it can be harmful because the patient remains at risk for hypersensitivity reactions to the antivenom. A study by Agarwal et al21 also confirmed that giving a higher dose of antivenom did not necessarily shorten the duration of ventilatory support of patients with severe envenomation. This trial had 55 patients with severe envenomation needing respiratory support, but unfortunately, species identification had been done for only three (kraits and cobras). Bungarus multicinctus is another venomous krait (Taiwanese or Chinese krait) prevalent in Southeast Asia. A case series from Vietnam in 60 consecutive patients with bites by this species showed that nearly 87% needed ventilatory support (mean duration, 8 days).22 However, this group was selected from an ICU and expected to have severe envenoming. These findings, therefore, cannot be generalized to B multicinctus bites as a whole. The mean duration of ICU stay was 12 days,
and mortality was 7%. Bungarus niger (greater black krait) is a venomous snake found in India and its eastern neighbors of Bangladesh, Burma, and Nepal. Case reports of venomous bites are less frequent compared with other kraits, but respiratory paralysis needing ventilatory support has been reported.23 Because specific antivenom may only be helpful in early stages of envenomation and anticholinesterases are not always useful (especially with krait bites), the major management strategy in elapid bite envenomation is supportive care, including mechanical ventilation. Unfortunately, when such services are limited, mortality is high. It can be even higher when there are other confounding factors, such as difficulty in accessing health care, delays in identifying a bite, and not seeking timely treatment due to cultural beliefs or a desire for indigenous medication. In a case series of 30 elapid bites in rural India (23 krait and seven cobra), Bawaskar and Bawaskar24 described a higher mortality rate than other studies, possibly for these reasons. The mortality in their sample was 40% for patients with krait bites and 43% for those with cobra bites. Four patients were dead on admission. Of those surviving, eight needed ventilatory support. Taipans are another group of extremely toxic elapids inhabiting the Australasian geographic area. A study of 166 patients with Papuan taipan (Oxyuranus scutellatus canni) bites showed that 37% needed mechanical ventilation.25 Neurotoxicity reached a peak within 24 h of the bite, and mean time to intubation was 13.5 h. Ventilatory support was needed in patients for up to 7.3 days (median, 3.6 days). Two deaths (1.2%) were attributed to respiratory arrest. The sole terrestrial venomous elapid snakes in the Americas are the coral species, which number . 70, but fatalities following coral snake bites are rare. However, case reports indicated that some species of coral snakes cause severe neurotoxic envenomation leading to respiratory paralysis.26 Studies do not report long-term complications following recovery from severe elapid envenoming, but patients may experience complications of prolonged mechanical ventilation. For example, a study in India assessing 59 snakebites (mostly krait bites) showed that 61% of the sample needed mechanical ventilation for a mean duration of 2.3 days (range, 1-6.2 days) and a rate of ventilator-associated pneumonia of 8.7%.27 In a retrospective audit of 533 patients in south India over 10 years, David et al28 showed that assisted ventilation was significantly associated with mortality (other pre-
1406 Special Features
dictors were acute kidney injury and hemotoxicity). Although part of this may be due to severe envenomation, complications of prolonged ventilation might have also added to the mortality rate. A randomized trial assessing two modes of overcoming endotracheal tube resistance in patients ventilated after snakebites (species not mentioned) showed that pressure support ventilation with automatic tube compensation would be a better option than pressure support ventilation alone because it leads to significantly faster weaning.29 Compared with elapid bites, reports of respiratory paralysis due to viper bites are few. In a series of 336 patients with Russell’s viper bits, Kularatne30 reported eight patients needing mechanical ventilation. Neurotoxicity resolved in these patients within 1 to 5 days. Ariaratnam et al31 studied 319 patients with Russell’s viper bites and observed respiratory muscle paralysis requiring mechanical ventilation in just seven (2%). Paret et al32 also described a case series of 37 envenomations with Vipera palaestine where respiratory compromise developed in two patients. Many other studies have described respiratory paralysis due to elapid and (rarely) viper bites. They are summarized in Table 1.33-53 Respiratory failure following sea snake bites has only been published as case reports.54 In summary, most reported cases of severe neurotoxic envenomation with respiratory paralysis are due to elapid bites. Kraits and cobras are the two most commonly cited elapids in this regard. Although the venom profile of some species has not been characterized, kraits usually have presynaptic neurotoxins that cause more permanent damage; hence, prolonged ventilatory support is needed. Cobra envenomation is relatively reversible because the toxin binds postsynaptically. When specific antivenom is available, early administration is recommended, but repeated dosing in absence of clinical improvement is not necessary because such manifestations are due to the already-bound venom, which is not affected by antivenom. Mechanical ventilation is needed in respiratory paralysis and is the most useful measure until the effect of venom wears off. Therefore, monitoring the progression of neurotoxicity in an ICU with objective measuring of vital capacity for early elective intubation can save lives. Anticholinesterases, such as neostigmine, may be useful when venom components predominantly reversibly bind to postsynaptic membranes. Because venom comprises a mixture of toxic proteins that may act on both sides of the membranes, the response to anticholinesterases may vary across
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] Respiratory Complications of Snakebites: Summary of Studies Not Discussed in Text
Respiratory paralysis Agrawal et al33
Prospective study of 14 patients admitted to an ICU with type 2 respiratory failure due to snakebite (species not mentioned). The median duration of ventilation (with antivenom serum treatment) was 17 h. Mortality was 7%.
Bawaskar and Bawaskar34
Prospective study of 91 cases of snakebite where 26 cases of respiratory failure were reported. In 20 instances, the snake was identi¿ed to be krait. The mortality rate was 38.6% (10 of 26).
Bawaskar et al35
A prospective study of 182 cases of snakebite in rural Maharashtra, India. There were 48 cases of krait bites, with 26 (54.2%) patients needing ventilatory assistance. The mortality rate was 14.6% (seven of 48). Of 41 cobra bites, 22 led to respiratory paralysis (53.6%), with a mortality rate of 9.1%.
In both cobra and krait envenomations, anticholinesterases were used, but any speci¿c response attributable to this treatment is not mentioned.
Brooks et al36
A retrospective analysis of 289 cases of rattlesnake envenomation in the United States noted respiratory compromise in 8% of patients, with only two patients (0.7%) requiring intubation.
Respiratory compromise following rattlesnake envenomations is reported but relatively rare.
Bucaretchi et al37
Retrospective analysis of 11 cases of coral snake bites (over a 20-y period) showed no development of respiratory failure.
The neurologic manifestations (myasthenia gravis, ptosis) showed an improvement with anticholinesterase administration in two patients.
Churchman et al38
A prospective study on clinical features of red-bellied black snake (Pseudechis porphyriacus) in Australia showed that of 57 patients with systemic envenoming, only one needed ventilatory support due to severe muscle weakness and myotoxicity.
Ha et al39
A controlled clinical trial in 81 patients of a novel antivenom against Bungarus multicinctus (until then treated with supportive therapy alone) in Vietnam showed that the antivenom therapy signi¿cantly reduced the neurologic complications, such as paralysis of limbs, diaphragm, and ptosis while reducing the duration of ICU stay and duration of mechanical ventilation. However, there was no signi¿cant reduction in the number of patients requiring mechanical ventilation between the two groups.
Johnston et al40
A prospective study of 14 patients with death adder bites (Acanthophis species) in Australia showed that only two needed mechanical ventilation for 17 and 83 h.
Kitchens and Van Mierop41
A retrospective case series of 39 coral snakebites over a 12-y period showed that only two had bulbar respiratory paralysis requiring mechanical ventilation.
The reaction rate for the antivenom was 7.4%.
As mentioned previously, respiratory paralysis with coral snakebites is rare. (Continued)
Lalloo et al
In a case series of seven con¿rmed Papuan black snake (Pseudechis papuanus) bites with systemic envenoming, one patient required assisted ventilation
Neurotoxic envenoming with respiratory failure is a possibility with this snake, although the number of reported cases are few.
Lalloo et al43
In a series of 18 con¿rmed death adder bites, ¿ve patients (28%) required intubation and mechanical ventilation.
Clinical improvement and reversal of features of neurotoxicity was observed in some patients after antivenom and anticholinesterase administration.
Pe et al44
A retrospective case series of envenoming by B multicinctus (n 5 8) showed evidence of neurotoxicity 2.5-6 h after the bite. Mortality due to respiratory failure was 37.5% (three of eight).
A retrospective analysis of 427 poisonous snakebites in Maharashtra, India, over a 10-y period showed neurotoxic manifestations resulting in respiratory paralysis from only cobra and krait bites. Of 71 patients with cobra bites, respiratory paralysis was observed in 36 (51%). Patients were treated with antivenom and anticholinesterases (neostigmine), with some showing an objective reversal of neurotoxicity. In the majority, the neurologic manifestations reversed in 8 h. Mortality was 18.3%. Of 42 patients with krait bites, 13 (31%) had respiratory failure. Neostigmine did not have a bene¿cial effect. Mortality was 7.1%.
Scop et al46
A retrospective case analysis of 23 tiger snake envenomations in Australia over a 16-y period showed that respiratory failure developed in only one patient who subsequently survived.
Seneviratne and Dissanayake47
A prospective study of 56 patients in Sri Lanka showed that 10 patients had severe envenomation with respiratory paralysis. Eight of them had krait bites and one had a Russell’s viper bite. The snake was unidenti¿ed in the remaining patient. All patients were treated with antivenom and mechanical ventilation and survived.
Sharma et al48
A retrospective analysis of all snakebites over 4 y in Chandigarh, India (n 5 142), showed that 86 patients had neurotoxic manifestations; all were bitten by cobras and kraits. Sixty-¿ve (76%) of these patients needed ventilatory support. Mortality was 3.5%.
Watt et al49
A prospective study of 39 envenomations with Philippine cobra (Naja naja philippinensis). Respiratory failure developed in 19, requiring mechanical ventilation. Mortality was 5%.
1408 Special Features
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Pulmonary edema and thromboembolism Bhagat et al50
Case report of pulmonary thromboembolism following a rattlesnake (Crotalus scutulatus) bite.
Chani et al51
Case report of pulmonary embolism following a Moroccan viper bite.
Karlson-Stiber et al52
A retrospective analysis of 231 Vipera berus bites in Sweden; pulmonary edema was a rarely reported complication of envenomation.
Thomas et al53
In a case series of 50 patients with Bothrops lanceolatus bites, 11 had thrombotic episodes due to envenomation (two with pulmonary embolism and nine with ischemic stroke and myocardial infarction).
individuals; thus, admission or transfer of a patient to a unit with facilities for assisted ventilation should not be delayed. Neostigmine should not be used in situations where it is likely to be ineffective, such as when venom proteins irreversibly bind to presynaptic membranes. Pulmonary Edema
Pulmonary edema following envenomation is another complication of snakebites55 and has been reported for both viper and elapid bites.21,56-58 Jeyarajah56 described a case series of Russell’s viper bites in 22 patients from Sri Lanka and found that pulmonary edema developed in eight (36.4%) and that all had acute renal failure. Four patients died, with the immediate cause of death attributed to severe pulmonary edema secondary to acute renal failure. Viper bites are known to cause neurogenic pulmonary edema as well.59 Joseph et al60 reported a case of pulmonary edema following a hump-nosed pit viper bite (Hypnale species) in Kerala, India. The venom of these vipers is known to cause acute renal failure, and pulmonary edema might have been secondary to this complication because the patient was dialysis dependent at the time this complication developed. Elapid bites likely cause pulmonary edema secondary to autonomic dysfunction and cardiotoxicity; however, most related studies are isolated case reports. Describing two brown snake (Pseudonaja textilis) envenomations in Australia, Henderson et al61 reported pulmonary edema secondary to cardiorespiratory failure and coagulopathy; both patients had succumbed to the illness. Agarwal et al62 also described a case of pulmonary edema secondary to cardiac involvement after a common krait bite in India
(B caeruleus). Cardiotoxicity following krait bites is rare, and its exact mechanism is yet unknown. During the period of severe envenomation in this particular patient, global hypokinesia was observed on echocardiography, which reversed with treatment. No alternative cause explained the pulmonary edema other than myocarditis secondary to venom cardiotoxicity. Pillai et al63 also reported an episode of pulmonary edema secondary to left ventricular dysfunction in a patient bitten by a Sind krait (Bungarus cf sindanus) in Maharashtra, India. Apart from a direct effect of envenomation, treatment with antivenom itself is known to precipitate pulmonary edema. However, such instances are rare. Singh et al64 reported an instance of noncardiogenic pulmonary edema in an 11-year-old boy secondary to antivenom therapy, which started 6 h after the infusion began. Overall, pulmonary edema is a known complication of both viper and elapid bites. However, the reported incidence in the literature is limited to a few case reports. Pulmonary edema from viper bites is mostly due to effects of acute kidney injury, and the rate may be grossly underestimated given that a significant number of Russell’s viper and hump-nosed viper envenomations lead to renal failure.65 Elapid bites may cause cardiogenic pulmonary edema secondary to cardiotoxicity, but the exact venom profile and mechanism of action are yet unidentified. Expectation and early detection is the key to avoiding death. Monitoring of patients with acute kidney injury and initiation of timely dialysis will save lives. Once pulmonary edema sets in, ICU care with ventilatory support (if required) is necessary. 1409
Thrombotic and Hemorrhagic Complications Aﬀecting the Lung
Thrombotic and hemorrhagic complications have been almost exclusively reported following viper bites. Most of the case reports are for the pit vipers of Bothrops species, which are endemic to Central and South America. Bothrops venom has procoagulant as well as anticoagulant properties, and usually, the manifestations are due to pulmonary hemorrhage secondary to anticoagulant properties. However, Estrade et al66 reported a case of pulmonary embolism following disseminated intravascular coagulation (DIC) due to Bothrops lanceolatus bite. Widespread thromboses following B lanceolatus are repeatedly observed and usually start 2 days after a bite, even in patients with moderate envenomation. Malbranque et al67 reported another case of a B lanceolatus bite where diffuse thrombotic microangiopathy developed, affecting the patient’s cerebral, pulmonary, myocardial, and mesenteric vasculature. Thrombosis attributed to B lanceolatus envenomation is believed to be due to vascular endothelial injury. In most patients, the tests for coagulopathy are normal or minimally deranged apart from thrombocytopenia. How vascular endothelial injury occurs in these bites is still unclear. One possibility is that the metalloproteinases in the venom are responsible. Some authors hypothesize that activation of von Willebrand factor may give rise to a microangiopathic thrombosis as seen with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome spectrum. Makis et al68 reported another instance where pulmonary embolism followed a viper bite; however, the patient had a rare form of congenital anemia (DiamondBlackfan anemia) and depended on transfusions with resulting iron overload. Iron overload itself is associated with a risk of thrombosis due to chronic oxidative damage to vessel endothelium.69 These background issues might have added to the patient’s prothrombotic state following envenomation. Hemorrhagic manifestations are well-known following viper bites because of the combined effects of consumptive coagulopathy, platelet dysfunction, and direct action of hemorrhagins (metalloproteinases) in viper venom.70 Regarding the lungs, pulmonary hemorrhages have been frequently reported following Bothrops species bites.70,71 Most local and hemorrhagic manifestations of viper bites are attributable to zinc metalloproteinases, which cause hemorrhage, hypofibrogenemia, and inhibition of platelet aggregation. Inhibitors to metalloproteinases have shown some promise in counteracting some of the deleterious effects of Bothrops asper venom,
1410 Special Features
confirming this hypothesis.72 In an animal model, several substances in B asper venom predisposed to bleeding tendency. Aspercetin caused a drop in platelet counts following injection, whereas jararhagin, a metalloproteinase, also contributed to this decline.73 Jararhagin has been demonstrated to induce pulmonary hemorrhage following injection in another animal study, and it is an important component in the venom of pit vipers.71 The proteinases Jararacussin-I and basparin-A, which are enzymes with procoagulant properties (serine proteinase and a prothrombin activator), also contribute to bleeding tendency by altering the checks and balances of clotting pathways. Almost all cases of pulmonary involvement with bleeding and thrombosis have been reported for Bothrops species bites in Central and South America. However, there are abundant case reports of viper bites causing bleeding manifestations in other organs from all over the world. DIC is a well-known complication of viper bites, which may at times cause a thrombotic microangiopathy affecting small vasculature, including that of the lungs. In one of the largest case series of Russell’s viper bites described (of 336 patients), Kularatne et al30 showed that 77% of patients had evidence of coagulopathy as demonstrated by a nonclotting 20-min whole-blood clotting test. However, the numbers with actual bleeding manifestations were less, and none showed frank pulmonary hemorrhage. DIC was observed in only seven patients (2%). The management of hemorrhagic or thrombotic manifestations is mainly supportive. However, when specific antivenom is available, it must be administered as early as possible. Unlike for neurotoxicity, repeated doses of antivenom may be necessary until the coagulopathy reverses. The 20-min whole-blood clotting test, which is a simple bedside test, is a good guide in this regard. Supportive care of bleeding tendency or DIC must always be carried out in consultation with a hematologist and would require frequent monitoring of prothrombin time, activated partial thromboplastin time, and serum fibrinogen levels for replacement of clotting factors. The lungs are a less likely target for organ damage due to hemotoxicity following viper bites. Physicians should be more alert to intracranial hemorrhages, infarctions, and renal damage, which are well-known causes for increased mortality and morbidity following viper bites.
Conclusions This review identifies three main themes with respect to pulmonary involvement from snakebites. The most well-known effect is respiratory paralysis, which is predominantly due to the neurotoxicity of elapid bites, such
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as those of cobras, taipans, and kraits. However, viper bites are also known to cause fatal respiratory paralysis, although it is not as prominent a feature as with elapid bites. Pulmonary edema is the second fatal manifestation of snakebites and can occur with both viper and elapid bites. This can be secondary to acute kidney injury or myocarditis due to cardiotoxicity of the venom. Lung hemorrhages and thromboses due to alteration of clotting mechanisms and DIC are mostly reported for pit vipers that are endemic to Central and South America. Management is twofold for all these complications and can be summarized as (1) administration of a specific antivenom (if available) and (2) supportive care. For respiratory paralysis and pulmonary edema, supportive care is the cornerstone to management, and repeated dosing of antivenom is unlikely to reverse the neurologic manifestations due to already-bound venom to nerve terminals. However, damage from coagulopathy is more likely to be averted by antivenom (supplemented by supportive care), and repeated dosing is recommended as monitored by tests of coagulation.
Acknowledgments Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/ organizations whose products or services may be discussed in this article.
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